Tocilizumab monotherapy nearly as effective as combination therapy

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Note that this meta-analysis demonstrated that a switch from ineffective DMARD therapy to tocilizumab was generally effective in the treatment of rheumatoid arthritis.

Similar effects were seen when investigators examined switches to tocilizumab monotherapy or tocilizumab+DMARD therapy.

Switching to tocilizumab from conventional synthetic disease-modifying antirheumatic drug (DMARD) therapy reduced disease activity in patients with rheumatoid arthritis (RA) who had an inadequate response to DMARDs, according to results from a meta-analysis. Efficacy was marginally better when patients switched to tocilizumab as an add-on to DMARDs compared with tocilizumab monotherapy, but severe side effects were more common with combination therapy, reported researchers from The Netherlands.

Add-on therapy is generally recommended for RA patients with an inadequate response to first-line DMARDs, but one third of patients have to discontinue DMARDs and initiate biologic monotherapy because of intolerance.

"Our results show that the efficacy of tocilizumab monotherapy is nearly equivalent to tocilizumab combination therapy in the management of active RA. Although the effect estimate for achieving disease activity score in 28 joints (DAS28) below 2.6 and American College of Rheumatology (ACR)50 response was significantly higher with the tocilizumab combination strategy, this is at the cost of a significant increase in the risk of serious adverse events when compared with tocilizumab monotherapy," wrote Xavier M. Teitsma, MSc, from University Medical Center Utrecht, and colleagues.

"Thus, if patients do not achieve the treatment target after initiating DMARD therapy because of intolerance, switching to tocilizumab monotherapy is a feasible option in clinical practice, whereas similar efficacy can be expected compared to inadequate responders to csDMARDs [conventional DMARDs] who switch to add-on tocilizumab combination therapy," they wrote in Arthritis Research & Therapy.

The investigators performed a systematic review and meta-analysis of 13 randomized clinical trials evaluating the safety and efficacy of tocilizumab monotherapy and combination therapy in a total of 6,679 patients with RA. The duration of symptoms ranged from 4 to 14 years in most studies, except in three in which patients had symptoms for 2 years or less. Most of the studies used methotrexate as the DMARD.

The proportion of patients with an ACR50 response was also significantly higher with both the tocilizumab monotherapy strategy (RR 1.87, 95% CI 1.19-2.95, P=0.007) and the tocilizumab combination strategy (RR 3, 95% CI 1.80-4.99, P<0.001) compared with DMARD therapy. Patients treated with tocilizumab as add-on therapy achieved an ACR50 response significantly more often than with the tocilizumab monotherapy strategy, although the authors stated that the effect estimate was "relatively small" (RR 1.14, 95% CI 1.03-1.26, P=0.008).

Similarly, the proportion of patients with an ACR70 response was significantly higher in those treated with tocilizumab monotherapy (RR 2.11, 95% CI 1.18-3.78, P=0.01) and tocilizumab combination therapy (RR 5.32, 95% CI 2.31-12.25, P<0.001) compared with DMARD therapy alone. There was no significant difference between the two tocilizumab strategies on ACR70 response.

Compared with patients receiving DMARD therapy alone, the risk estimate for experiencing one or more adverse events was higher for both the group receiving tocilizumab monotherapy (RR 1.08, 95% CI 1.01-1.15, P=0.03) and those receiving tocilizumab combination therapy (RR 1.12, 95% CI 1.06, 1.18, P<0.001). There was no significant difference between the tocilizumab monotherapy and tocilizumab combination strategies on this outcome.

In sensitivity analyses including only studies that reported 24-week results, the risk estimates of the efficacy outcomes were relatively unchanged; however, the pooled risk for serious adverse events changed from being significant (RR 1.40, 95% CI 1.03-1.92, P=0.03) to nonsignificant (RR 1.34; 95% CI 0.79-2.27, P=0.27) -- "indicating the two tocilizumab strategies were equally safe," the authors wrote.

Because both tocilizumab strategies were superior to methotrexate in achieving remission, the study "endorses the immediate initiation of tocilizumab in early rheumatoid arthritis, with or without methotrexate, when used in a treat-to-target approach, including tapering of medications when remission is achieved."

Regarding potential limitations, Teitsma and colleagues pointed to the heterogeneity of DMARD therapy in the studies included and the different treatment durations.

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